Established amyloid-β pathology is unaffected by chronic treatment with the selective serotonin reuptake inhibitor paroxetine

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  • Maurizio Severino, Syddansk Universitet
  • ,
  • Mithula Sivasaravanaparan, Syddansk Universitet
  • ,
  • Louise Olesen
  • ,
  • Christian U. von Linstow, Syddansk Universitet
  • ,
  • Athanasios Metaxas, Syddansk Universitet
  • ,
  • Elena V. Bouzinova
  • Asif Manzoor Khan, Syddansk Universitet
  • ,
  • Kate L. Lambertsen, Syddansk Universitet, Odense Universitetshospital
  • ,
  • Alicia A. Babcock, Syddansk Universitet
  • ,
  • Jan Bert Gramsbergen, Syddansk Universitet
  • ,
  • Ove Wiborg, Aalborg University
  • ,
  • Bente Finsen, Syddansk Universitet

Introduction: Treatment with selective serotonin reuptake inhibitors has been suggested to mitigate amyloid-β (Aβ) pathology in Alzheimer's disease, in addition to an antidepressant mechanism of action. Methods: We investigated whether chronic treatment with paroxetine, a selective serotonin reuptake inhibitor, mitigates Aβ pathology in plaque-bearing double-transgenic amyloid precursor protein (APP)swe/presenilin 1 (PS1)ΔE9 mutants. In addition, we addressed whether serotonin depletion affects Aβ pathology. Treatments were assessed by measurement of serotonin transporter occupancy and high-performance liquid chromatography. The effect of paroxetine on Aβ pathology was evaluated by stereological plaque load estimation and Aβ42/Aβ40 ratio by enzyme-linked immunosorbent assay. Results: Contrary to our hypothesis, paroxetine therapy did not mitigate Aβ pathology, and depletion of brain serotonin did not exacerbate Aβ pathology. However, chronic paroxetine therapy increased mortality in APPswe/PS1ΔE9 transgenic mice. Discussion: Our results question the ability of selective serotonin reuptake inhibitor therapy to ameliorate established Aβ pathology. The severe adverse effect of paroxetine may discourage its use for disease-modifying purposes in Alzheimer's disease.

Original languageEnglish
JournalAlzheimer's and Dementia: Translational Research and Clinical Interventions
Volume4
Pages (from-to)215-223
Number of pages9
DOIs
Publication statusPublished - 1 Jan 2018

    Research areas

  • 5,7-dihydroxytryptamine, Alzheimer's disease, Autoradiography, Cerebral amyloidosis, Monoamine, Neocortex, Selective serotonin reuptake inhibitor, Serotonin, SERT occupancy, Stereology, Transgenic mouse model, [H]DASB

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